kawabata all in one 20150717.ppt [互換モード]›‹白質複合体予測 MODELLER,HOMCOS ZDOCK, HADDOCK, … 低分子―タンパク質複合体予測 MODELLER,HOMCOS, fkcombu

507

Allinone(NBDC,DBCLS,PDBj,DDBJ)

[email protected]

1

(1)

(2)

(Structural Genomics)

(3)SNP

DnsSNPHOMCOS

HOMCOS

HOMCOS

( SeqID 44%)

(1fueA) (1ag9A)

SeqID = 44 %

RMSD = 1.2

1fueA 2:GKIGIFFGTDSGNAEAIAEKISKAIG--NAEVVDVAKASKEQFNGFTKVILVAPTAGAGD:59***** * ** * ** * * * * * * ** *** * ** *

1ag9A 2:AITGIFFGSDTGNTENIAKMIQKQLGKDVADVHDIAKSSKEDLEAYDILLLGIPTWYYGE:61

1fueA 60:LQTDWEDFLGTLEASD-FANKTIGLVGLGDQDTYSETFAEGIFHIYEKAK--AGKVVGQT:116* ** ** *** * * * * *** * * * * **

1ag9A 62:AQCDWDDFFPTLE-EIDFNGKLVALFGCGDQEDYAEYFCDALGTIRDIIEPRGATIVGHW:120

(

RMSD

(1ag9A)

NADPH P450 C (1ja1A2)

CheY(3chy)

(1d4aA)

44%, 1.2

8%, 4.4

(1fueA)

N

C 14%, 3.2

C

N

12 3 4 5

CNN

C

N

C

N

C

BLAST

PSI-BLAST

100

30%

BLASTE-value < 0.0001

PSI-BLASTE-value < 0.0001

0102030407025 15 535

(Sequence Identity)

(1)(DALIZMATRASRdis)(2)PSI-BLASTSeqID>=15%(3)(4)(5)(6)

50608090

LNVANGKSVIGPALLEEVWGSRD

M

N

I

AD

G

SV

V

GA L

QE

A W

FT

QD

PT

R

L

N

V

AN

G

SV

I

GL L

EE

V W

FS

QD

PA

R K

LNVANGKSVIGPALLEEVWFS-RD* * * ** ** * * ** **

MNIADG-SVVGPTALQEAWFTQRD

: .

BLAST, , . MODELLER, FAMS, .

(MODELLER)

Sequence ALIMSTKGFVSStructure LLLM---GFIT

(1)

(2)

Sequence AYVINDStructure AFVVTD AFVVTD AYVIND

MODELLER :http://www.salilab.org/modeller/modeller.html

MODELLER (http://www.salilab.org/modeller/)

[]

[NMR]

SeqID = 50 %

SeqID = 30 %

Ab initio

[]

SeqID = 100 %

Baker, D., Sali, A. Science (2001), 294, 93-96

AbinitioDe novo

MODELLER,SWISSMODEL ROSETTA,EVfold,

MODELLER, HOMCOS ZDOCK,HADDOCK,

MODELLER, HOMCOS,fkcombu

DOCK,AutoDock, sievgene,Glide,

PDBj1) GooglePDBj 2) PDBjSequence Navigator

3) [Search by sequence]UniProtCALL5_HUMAN

4) PDBBLASTPDB1ahrAsequence identity 51%

CALL5_HUMAN(Calmodulin-like protein 5)

UCSFChimeraModeller

Calmodulin (1ahr) Calmodulin-like protein 5(1ahr)

UCSF Chimera() ModellerGUI

Ca2+

UCSF ChimeraModeller 2015/6/13H27 PDBjing PDBj(http://pdbj.org/info/previous-workshop)

UCSFChimera

5000 RasMol, UCSF Chimera, PyMOL

[Tools][Structure Editing][AddH] [Tools][Structure Editing][Add Charge]

Auto Dock Vina [Surface/Binding Analysis][AutoDock Vina]

[Surface/Binding Analysis][ViewDock]

Cyclin-dependent protein kinase (CDK2)

ADPSubstrate PeptidePKTPKKAKKL

Cyclin A2

(1)

(2) 3D Complex of CDK2ADPCyclin A2 + Peptide(PDBcode:3qhw)

:TemplatebasedModeling

V

W

E

IE

I

N

GT

L

V

L

K

Q

V

F

TF

AT

V

F

E

IK

I

Q

GT

L

I

L

K

E

V

F

TF

AG

T

A L

Q

AE

LL

KL

K

VG

WK

D

T

T

A L

Q

LQ

LL

KL

K

IG

FK

D

T

V

F

E

IK

I

Q

GT

L

V

W

E

IE

I

N

GT

L

TGWVEIEINL..

TGWVEIEINL..

QLVVKTFAFT..

IVAWGKTDLQAE..

:TemplatebasedDocking

T

A L

Q

LQ

LLK

L

K

IGF

K

DT

VF

E

IKIQ

GT

L

I

L

K

EV

F

TF

AG

VW

E

IEIQ

GT

L

I

L

K

TV

F

TF

A

GD

I

L

K

TV

F

TF

A

G

VW

E

IEIQ

GT

L

D

VF

E

IKIQ

GT

L

I

L

K

EV

F

TF

AG

VW

E

IEIQ

GT

L

I

L

K

TV

F

TF

A

GD

S

A L

Q

LQ

LLK

L

K

IAS

DT

T

A L

Q

LQ

LLK

L

K

IGF

K

DT

S

A L

Q

LQ

LLK

L

K

IAS

DT

S

A L

Q

LQ

LLK

L

K

IAS

DT

-

50 %() 10%

Ca2+

Ca2+

(%) (%)

(%)

(%)

10%:Ca2+

HOMCOS :

PDB

A

B

PDBBLASTKCOMBU

MYB

HRXCrebbp

MYB

MRE-1

MRE-1

http://homcos.pdbj.orgHOMCOS

PDBBLAST

BLASTKCOMBU PDB

BLAST BLAST

BLAST KCOMBU

>1vwg_A

>1jsu_B

2g9xA1w98A1fq1B:

1vwg_1 A1 B12g9x_1 A1 B1:

KCOMBU

BLAST

TGWVEIEINL

SHLC39GBC:

SHL

GBC

C39

1vwg_1 A1 B12g9x_1 A1 B1:

PDB

PDB

CDK31) GoogleHOMCOS 2)

3) IDCDK3_HUMAN[SEARCH]

(i) PDB_ID+ (ii) PDB(iii) ID UniProt ID/AC

INSDCRefSeqprotein_id,(iv)

CDK3_HUMAN (Cyclin-dependent kinase 3)

ID PDB

HOMCOS

MEEPQSDPSVEPPLSQETFS

UniProtID P53_HUMAN []_[]

UniProtAC P04637Q15086

ACID

INSDC(DDBJ,EMBLEBI,NCBI)protein_id

AAG28785.1ABA29753.1EAW90143.1

DNAFEATURESCDSIDDDBJDAD

RefSeqprotein_id

NP_000537.3NP_001119584.1XP_011525440.1

NCBIdbSNP

INSDCDNAprotein_id

(CDK3)

E-value

(CDK3)Sequence-replaced 3D model

(CDK3_HUMAN)(1fin_C_1

ModellerModeller

CDK3CDK2

ContactBar(CDK3)

(%)

(CDK3)

CDK3CDK2

Cyclin A2

(CDK3)

b

Sequence-replaced modelModeller

CDK3

Cyclin A2

ContactBar(CDK3)

(%)

4QE, 4SPPDB

(CDK3)

4QE

(CDK3)

b

CDK3CDK2

Sequence-replaced modelModeller

SiteTable

UniProt(Feature Table)

(H:E:)

(%)

(1) acc

(2) observed aaSIFT score

3(CDK3)

PDBID3

(CDK3)

Cyclin A2

Met(Asn)

CDK3(CDK2)

SPIC_HUMAN

SPIC_HUMAN (Transcription factor Spi-C)

(SPIC)

PDB(Biological Unit) assembly_id=1

(SPIC)

PDB(Biological Unit) assembly_id=1

assembly_id=1

DnsSNP

3DnsSNP:nsSNP(1)1) GoogleNBDC 2)

3) Human Variation DB

3DnsSNP:nsSNP(2)4) Browse by disease name 5) Adrenoleukodystrophy

Wikipedia:Adrenoleukodystrophy, ALD1ALD

12XALDXX2X150%2

3DnsSNP:nsSNP(3)

dbSNP RefSeqID

3DnsSNP:nsSNP(4)

NP_000245.2919D(Asp)G(Gly) D

3DnsSNP:3D(1)1) GoogleHOMCOS 2)

3) IDNP_000245.2[SEARCH]

ID

NP_000245.2 919D(Asp)G(Gly)

3DnsSNP:3D(2) NP_000245.2 919D(Asp)G(Gly)

METH_HUMAN Methionine synthase, 5-methyltetrahydrofolate--homocysteine methyltransferase, Vitamin-B12 dependent methionine synthase. GN Name=MTR;

-!- FUNCTION: Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity). {ECO:0000250}. -!- CATALYTIC ACTIVITY: 5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine. CC -!- COFACTOR: Name=methyl(III)cobalamin; Xref=ChEBI:CHEBI:28115; -!- COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};Note=Binds 1 zinc ion per subunit. {ECO:0000250}; -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.


COB:CO-METHYLCOBALAMIN

Co

919D(1bmtA893N)

919DCOB

COB

919D

COB

P_000245.2919DG

Adrenoleukodystrophy,ALDnsSNP(NP_000245.2919DG)

D14%G

55.1

COBG

E

IK

I

Q

GT

L

F

T

I

K

E

V

FV

L

F

AG

>1vwg_A

>1vwg_B

>2g9x_A

1vwgA2g9xA8atcA1fq5A:

1vwg_1 A1 B12g9x_1 A1 B11jsu_1 A1 B18atc_2 A1 B12fi5_1 E2 I1:

BLAST

BLAST

1vwg_1 A1 B1

V

W

E

IE

I

N

GT

L

V

L

K

Q

V

F

TF

AT

E

IK

I

Q

GT

L

F

T

I

K

E

V

FV

L

F

AG

TGWVEIEINL...

QLVVKTFAFT...

1vwgB2g9xB2fi5I2eufA:

B

A

Template-based Model(Sequence-replaced model)

V

W

E

IE

I

N

GT

L

T

V

K

Q

V

F

L

F

A

TV

W

E

IE

I

N

GT

L

T

V

K

Q

V

F

L

F

A

T

Template-based docking

B

A

or

or

orPDB

(21) GoogleHOMCOS 2)

CDK5_HUMAN Cyclin-dependent proten kinase 5CCNB1_HUMAN G2/mitotic-specific cyclin B1

3) AUNIPROT_IDCDK5_HUMANBUNIPROT_IDCCNB1_HUMAN

(i) PDB_ID+ (ii) PDB(iii) ID UniProt ID / AC

INSDCRefSeqprotein_id,(iv)

CDK5_HUMAN CCNB1_HUMAN

sequence-replaced 3D model

sequence-replaced modeltemplate 3D structure

ABPDBBLAST

Modeller(Win8)[1]

HOMCOSCDK5_HUMANCCNB1_HUMAN

Modeller

(model_complex.py) (alignment_complex.ali),(1h27_A_1_B_1.pdb)C:Usersguest01Downloads

Modeller(Win8)[2]

(4)

(5)MModeller

(6)

(7) cd []

cd C:Usersguest01Downloads

(8)dir

Modeller(Win8)[3]

(9) mod9.14 []Modellermod9.14 model_complex.py

(10)dirquery_complex.B99990001.pdbChimera

1) GoogleHOMCOS 2)

4au8A Cyclin-dependent proten kinase 52b9rA G2/mitotic-specific cyclin B1

3) APDB_ID4au8, CHAIN_IDABPDB_ID2b9r, CHAIN_IDA

(i) PDB_ID+ (ii) PDB(iii) UniProt ID (iv)

(2

ABPDBBLAST

4au8A (CDK5) 2b9rA (CCNB1)

template-based 3D docking model

sequence-replaced modeltemplate 3D structuretemplate-based 3D docking model

T

A L

Q

LQ

LLK

L

K

IGF

K

DT

>1vwg_A

2g9xA1jsuA1fq5A8atcA:

PDB

2g9x A1 B1(SHL)1jsu A1 B1(C39)8atc A1 B1(PLP)2fi5 E2 I2(ATP):

KCOMBU

BLAST

SHLC39GBC:

PDB

T

A L

Q

LQ

LLK

L

K

IGF

K

DT

fkcombu

SHL

GBCC39

SHL

TVAWGKTDLQL

2g9x_A1 B1

T

A L

QA E

LLK

L

R

VG WK

DT

or

T

A L

QA E

LLK

L

R

VG WK

DT

T

A L

Q

AE

LLK

L

R

VGW

K

DT

Template-based Model(Sequence-replaced model)

Template-based docking

>1vwg_B

>2g9x_A

or

2)

3) PROTEINUNIPROT_IDCDK3_HUMANCOMPOUNDPDB three letter ligand codeIRE

Iressa/Gefitinib (IRE)

1) GoogleHOMCOS

PDBBLAST PDBKCOMBU

(IRE) (DTQ)

(DTQ)

(IRE)

Documents

kawabata all in one 20150717.ppt [互換モード]›‹白質複合体予測 MODELLER,HOMCOS ZDOCK, HADDOCK, … 低分子―タンパク質 複合体予測 MODELLER,HOMCOS, fkcombu

kawabata all in one 20150717.ppt [互換モード]›‹白質複合体予測 MODELLER,HOMCOS ZDOCK, HADDOCK, … 低分子―タンパク質複合体予測 MODELLER,HOMCOS, fkcombu